The first line of defense for the sensitive and critical functions of the eye is the eyelid. This elegant structure contains a set of antagonistic muscles: the orbicularis oculi, which closes the eye, and the levator palprebrae superioris, which opens the eye. The lid exhibits two basic behaviors. The blink, which closes the eye for protection and spreads the tear film, is initiated by concomitant orbicularis excitation and levator inhibition. Saccadic lid movements, in which the lid compensates for vertical saccades, are solely a function of the levator. Dysfunction of lid movement results from numerous disease states, including blepharospasm, Grave's disease and Wallenberg's syndrome. In addition, the blink is an important model for CNS mechanisms in learning. There is, however, surprisingly little known about the basic neural circuits directing lid movements. Thus, our capacity to understand control of lid movement and its impairment in disease is significantly compromised. This proposal applies a multidisciplinary approach to define these basic lid circuits. Specifically, the pathways that subserve saccadic lid movements, blinks associated with orienting movements and trigeminally evoked blinks will be investigated in the cat. Putative inputs to lid motoneurons will be identified via retrograde transport and further characterized by combining retrograde identification with immunocytochemical localization of inhibitory transmitters. Selected inputs will be definitively demonstrated by combining anterograde transport techniques with the intracellular straining of antidromically identified lid motoneurons. Analysis using the electron microscopic level will provide identification of anterogradely labelled terminals synapsing on intracellularly stained lid motoneurons. To assess how these findings relate to the primate organization and identify the circuitry changes that underlie the loss of the retractor bulbi muscles, the anatomical experiments will be extended to macaque monkeys and include superior rectus motoneurons. Thus, the anatomy and transmitter specificity of the lid control circuitry will be determined in a functional context.